Anther development: basic principles and practical applications.

MOTIVATION: Identifying regulatory elements in various chromosomal regions that influence gene expression is a fundamental challenge in epigenomics, with profound implications for understanding gene regulation and disease mechanisms. The advent of paired single-cell RNA sequencing and single-cell ATAC sequencing has created unprecedented opportunities to address this challenge by enabling simultaneous profiling of gene expression and chromatin accessibility at single-cell resolution. However, the inherent signals between them are weak due to the highly sparse and noisy nature of data. RESULTS: This article proposes single-cell meta-Path based Omics Embedding (scPOEM), a novel embedding method that jointly projects chromatin accessibility peaks and expressed genes into a shared low-dimensional space. By integrating the relationships among peak-peak, peak-gene, and gene-gene interactions, scPOEM assigns closer representations in the embedding space to related peak-gene pairs. Our experiments demonstrate that scPOEM generates stable representations of peaks and genes, outperforms existing methods in recovering biologically meaningful peak-gene regulatory relationships and enables new insights in subgroup and differential analysis of gene regulation. These results highlight its potential to uncover gene regulatory mechanisms and enhance the understanding of transcriptional regulation at single-cell resolution. AVAILABILITY AND IMPLEMENTATION: The source code of scPOEM is available at https://github.com/Houyt23/scPOEM. The datasets can be obtained from the 10× Genomics (https://www.10xgenomics.com/datasets/pbmc-from-a-healthy-donor-granulocytes-removed-through-cell-sorting-10-k-1-standard-1-0-0) and GEO database under access codes GSE194122 and GSE239916.

Gene Expression Regulation↗

PubMed1996

p53 and translational control.

The tumor suppressor p53 plays a role in mediating a G1 arrest (for example, in response to DNA damage), in the cellular commitment to apoptosis and in suppression of transformation. The mechanism of action of p53 in each of these biological outcomes is likely to be overlapping. Current data indicate that p53 functions as a sequence specific transcriptional activator. p53 can also repress transcription from certain promoters. One way in which p53 mediates a G1 arrest after DNA damage appears to be clear. Cells exposed to ionizing radiation show elevated levels of p53 protein. The increase in p53 levels is thought to be responsible for the increase in the cyclin-dependent kinase (cdk) inhibitor p21 mediated through the p53 binding sites in the p21 promoter. With regard to the ability of p53 to suppress transformation, there is data suggesting that p53 functions other than, or in addition to, its transcriptional activation function may be necessary. Similar data exist for p53-dependent apoptosis. Recently a role for p53 at another level of gene regulation, namely, translational regulation has been proposed. p53 associates with various components of the translation machinery and has been implicated in the translational regulation of both the p53 and CDK4 mRNAs. Here we will summarize the evidence suggesting a role for p53 in translation and how this regulation might be achieved.

Gene Expression Regulation↗

PubMed1995

Selective regulation of TrkA and TrkB receptors by retinoic acid and interferon-gamma in human neuroblastoma cell lines.

Trk receptors are a family of genes implicated in the survival, differentiation, and growth of certain neurons and tumors of the nervous system. A better understanding of the regulation of Trk receptors is relevant for developmental and oncological studies. Human neuroblastoma (NB) cell lines constitutively express low levels of TrkA mRNA, while TrkB mRNA is not readily detectable. Differentiation of NB cells is accompanied by a differential modulation of Trk expression in human NB cells. Nanomolar concentrations of RA induce a stable increase of TrkB mRNA. A transient induction of TrkA mRNA levels requires micromolar concentrations of RA. Induction of both TrkA and TrkB mRNA does not require new protein synthesis. However, RA-induced TrkB mRNA expression is transcriptionally regulated, while the transient RA-induced increase of TrkA mRNA is a consequence of extended mRNA stability. Interferon gamma (IFN-gamma) selectively increases TrkA mRNA without affecting TrkB mRNA levels. Similar to RA, IFN-gamma does not modify the transcriptional rate of TrkA mRNA, but rather increases TrkA mRNA stability. Thus, RA and IFN-gamma differentially regulate TrkA or TrkB expression in the same cell type by predominantly transcriptional (TrkB) or post transcriptional (TrkA) mechanisms. Such experiments indicate the complexity of Trk mRNA regulation and also indicate compounds that may affect neurotrophin responsiveness in developing neural cells.

Gene Expression Regulation↗